Navigating the Challenges of Cyclosporine as an Alternative to Rifampicin as an OATP1B Index Inhibitor.

Rifampicin is a widely employed index inhibitor to assess the impact of organic anion transporting polypeptide 1B (OATP1B) inhibition on investigational drugs. The observation of nitrosamines in certain drug products, including rifampicin, has impacted the conduct of clinical drug-drug interaction (DDI) studies with rifampicin drug products. Cyclosporine is a recommended alternative to assess in vivo OATP1B activity; however, challenges exist in its use due to pharmacokinetic (PK) variability and non-selective inhibition of other drug disposition mechanisms.